Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatic arterial infusion (HAI) chemotherapy as treatment for human colorectal liver metastases is promising, but not entirely satisfactory. Improved drug delivery during HAI may be achieved by manipulating the different control mechanisms of normal versus tumour blood vessels. The peptidergic/aminergic innervation of vessels in normal liver and in two animal models of liver metastasis (Lister Hooded rat with syngeneic MC28 sarcoma; athymic (nude) rat with human HT29 carcinoma) was investigated to assess the suitability of these models for future pharmacological studies. Normal liver and metastases were studied immunohistochemically for the presence of protein gene product 9.5 (PGP), neuropeptide Y (NPY), tyrosine hydroxylase (TH), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and substance P (SP). Perivascular innervation was also examined by transmission electron microscopy. In Lister rat normal livers, perivascular immunoreactive nerve fibres containing PGP, NPY, TH, CGRP and SP were observed around the interlobular blood vessels near the hilum and in the portal tracts. The highest density was seen for PGP, followed in decreasing order, by NPY, TH, CGRP and SP. VIP-immunoreactive nerves were absent. No immunoreactive nerves were observed in the hepatic lobule. In athymic rat livers, the pattern of innervation was similar, except that SP immunoreactivity was more sparse. No perivascular immunoreactive nerves were observed in either MC28 or HT29 tumours. Electron microscopy confirmed the absence of perivascular nerves. Smooth muscle cells were not observed in tumour blood vessel walls. These results are comparable with previous observations on human liver metastases and suggest that the animal models may be suitable for pharmacological studies on vascular manipulation of HAI chemotherapy.
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PMID:Blood vessels in liver metastases from both sarcoma and carcinoma lack perivascular innervation and smooth muscle cells. 924 51

Hypocretins (Hcrts) are recently discovered peptides linked to the human sleep disorder narcolepsy. Humans with narcolepsy have decreased numbers of Hcrt neurons and Hcrt-null mice also have narcoleptic symptoms. Hcrt neurons are located only in the lateral hypothalamus (LH) but neither electrolytic nor pharmacological lesions of this or any other brain region have produced narcoleptic-like sleep, suggesting that specific neurons need to be destroyed. Hcrt neurons express the Hcrt receptor, and to facilitate lesioning these neurons, the endogenous ligand hypocretin-2/orexin B (Hcrt2) was conjugated to the ribosome-inactivating protein saporin (SAP). In vitro binding studies indicated specificity of the Hcrt2-SAP because it preferentially bound to Chinese hamster ovary cells containing the Hcrt/orexin receptor 2 (HcrtR2/OX(2)R) or the Hcrt/orexin receptor 1 (HcrtR1/OX(1)R) but not to Kirsten murine sarcoma virus transformed rat kidney epithelial (KNRK) cells stably transfected with the substance P (neurokinin-1) receptor. Administration of the toxin to the LH, in which the receptor is known to be present, eliminated some neurons (Hcrt, melanin-concentrating hormone, and adenosine deaminase-containing neurons) but not others (a-melanocyte-stimulating hormone), indicating specificity of the toxin in vivo. When the toxin was administered to the LH, rats had increased slow-wave sleep, rapid-eye movement (REM) sleep, and sleep-onset REM sleep periods. These behavioral changes were negatively correlated with the loss of Hcrt-containing neurons but not with the loss of adenosine deaminase-immunoreactive neurons. These findings indicate that damage to the LH that also causes a substantial loss of Hcrt neurons is likely to produce the multiple sleep disturbances that occur in narcolepsy.
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PMID:Hypocretin-2-saporin lesions of the lateral hypothalamus produce narcoleptic-like sleep behavior in the rat. 1154 37

We investigated some neurochemical changes that take place in the spinal cord dorsal horn in a mouse model of neuropathic cancer pain. The model was produced by inoculation of Meth-A sarcoma cells to the vicinity of the sciatic nerve, which resulted in growth of a tumor mass embedding the nerve. Hind paw-lifting, a behavioral sign of spontaneous pain, was at maximum on Day 18, but decreased thereafter. The decrease was likely caused by progression of motor paralysis. On Day 18, thermal and mechanical pain thresholds of the affected paw were significantly increased. Histologically, the sciatic nerve presented damages to both unmyelinated and myelinated fibers on Day 18, which were more pronounced on Day 25. In the spinal cord, c-Fos-positive cells were significantly increased in the superficial and deep layers on Day 18. The number of c-Fos-positive cells in the superficial layer correlated with the duration of paw-lifting. The increase in c-Fos-positive cells was still present on Day 25 despite decreased paw-lifting. Substance P and calcitonin gene-related peptide were up-regulated on Day 18 but down-regulated on Day 25. A marked up-regulation of dynorphin A (DynA) was present on Day 18 and persisted through Day 25. Our model caused progressive damage to the sciatic nerve and presented spontaneous pain-behavior while the paw became hyposensitive to mechanical and thermal stimuli. Since the up-regulation of DynA in the dorsal horn persisted and paralleled the increase in c-Fos-positive cells, the release of DynA may be associated with spontaneous pain in our model.
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PMID:Change of dorsal horn neurochemistry in a mouse model of neuropathic cancer pain. 1573 48

Cancer pain impairs the quality of life of cancer patients, but opioid analgesics can not only cause inhibition of respiratory function, and constipation, but also other significant side effects such as addiction and tolerance that further decrease quality of life. Thus, in the present study, the effects of electro-acupuncture treatment (EA) on mechanical allodynia were examined in cancer pain mouse model. In order to induce neuropathic cancer pain model, S-180 sarcoma cells were inoculated around the sciatic nerve of left legs of Balb/c mice. The mass of S-180 cancer cells embedded around sciatic nerve in a time course was confirmed by Magnetic Resonance Imaging (MRI) scanning. Mechanical allodynia was most consistently induced in mouse sarcoma cell line S-180 (2 x 10(6) sarcoma cells) treated group among all groups. EA stimulation (2Hz) was daily given to ST36 (Zusanli) of S-180 bearing mice for 30 min for 9 days after S-180 inoculation. EA treatment significantly prolonged paw withdrawal latency from 5 days after inoculation as well as shortened cumulative lifting duration from 7 days after inoculation compared with tumor control. In addition, the overexpressions of pain peptide substance P in dorsal horn of spinal cord were significantly decreased in EA treated group compared with tumor control on Day 9 after inoculation. Furthermore, EA treatment effectively increased the concentration of beta endorphin in blood and brain of mice more than tumor control as well as normal group. The concentration of beta-endorphin for EA treatment group increased by 51.457% in blood 12.6% in brain respectively, compared with tumor control group. These findings suggest that S-180 cancer pain model can be a consistent and short time animal model and also EA treatment can be an alternative therapeutic method for cancer pain via decreased substance P and increased beta endorphin.
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PMID:Substance P and beta endorphin mediate electroacupuncture induced analgesic activity in mouse cancer pain model. 1971 73